Effect of Fluvastatin on Brown Fat Activity

NCT ID: NCT03189511

Last Updated: 2018-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-31

Study Completion Date

2018-02-19

Brief Summary

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The purpose of this study is to elucidate the effects of Fluvastatin on brown adipose tissue activity in humans.

Detailed Description

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Statins, inhibitors of cholesterol biosynthesis, act by inhibiting the enzyme of the mevalonate pathway. Although the clinical benefits of statins are undisputable, they have been shown to increase insulin resistance and incidence of type 2 diabetes mellitus, the mechanism of which is currently not clear.

The main function of brown adipose tissue (BAT) is non-shivering thermogenesis (i.e. heat production through energy dissipation) in brown adipocytes. There has been a growing interest in BAT as a novel therapeutic approach to increase energy expenditure in order to facilitate weight-loss and increase insulin sensitivity.

BAT activity will be assessed using calorimetric test and \[18F\]-Fluorodeoxyglucose (FDG) positron emission tomography (PET).

We speculate that statins inhibit BAT function and that this mechanism may contribute to the above mentioned increase in insulin resistance.

Conditions

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Adipose Tissue, Brown Insulin Resistance Clinical Trial

Keywords

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Brown Adipose Tissue Brown Fat Fluvastatin Prospective Clinical Trial

Study Design

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Intervention Model

SEQUENTIAL

Open-label non-randomized historic control (before-after) trial
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Experimental

Volunteers receive calorimetric tests and FDG PET scans pre and post 2 weeks of Fluvastatine.

Group Type EXPERIMENTAL

Fluvastatin

Intervention Type DRUG

Fluvastatin 40 mg twice daily per mouth for 14 days.

Interventions

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Fluvastatin

Fluvastatin 40 mg twice daily per mouth for 14 days.

Intervention Type DRUG

Other Intervention Names

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Lescol

Eligibility Criteria

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Inclusion Criteria

* Male volunteers (18-40 y)
* body mass index 19 to 27 kg/m²
* Fluent in German or English

Exclusion Criteria

* Regular physical exercise of more than \>150 min of exercise per week.
* Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
* Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
* Clinically indicated intake of the following medications: Corticosteroids, CYP3A4-Inhibitors (Itraconazol, Voriconazol, Fluconazol, Clarithromycin, Erythromycin, Indinavir, Nelfinavir, Ritonavir, Grapefruit juice), Beta-Blocker, Neuroleptics, Tricyclic Antidepressants,
* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present study,
* Participation in another study involving ionizing radiation in the same year,
* Previous enrolment into the current study,
* Enrolment of the investigator, his/her family members, employees and other dependent persons,
* MRI contraindications: Not MRI-compatible metal in the body, cardiac pacemaker, History of surgery with possible metal clips/parts still in the body, claustrophobia.
* Resting pulse rate \> 70 bpm
* Known arterial hypertension or resting blood pressure \> 130/80 mmHg.
* frequence corrected QT-time (QTc) \>430 ms
* Serum creatinine \> 1.5x upper limit of norm (ULN), i.e.\> 145 µmol/L
* creatine kinase \> 1.5x ULN, i.e. \> 300 U/L
* aspartate transaminase (ASAT) \> 1.5x ULN, i.e. \> 51 U/L
* alanine aminotransferase (ALAT) \> 1.5x ULN, i.e. \> 88 U/L
* Hypothyroidism
* Vitamin D deficiency, Vitamin D3 \< 25 nmol/L
* Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
* Known tendency to form keloids (hypertrophic scar tissue)
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Basel

OTHER

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Irene A Burger, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

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University Hospital of Zurich, PET/MR Center

Schlieren, Canton of Zurich, Switzerland

Site Status

University Hospital of Basel

Basel, , Switzerland

Site Status

Countries

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Switzerland

References

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Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 2015 Jan 6;21(1):33-8. doi: 10.1016/j.cmet.2014.12.009.

Reference Type BACKGROUND
PMID: 25565203 (View on PubMed)

Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 Jun 22;305(24):2556-64. doi: 10.1001/jama.2011.860.

Reference Type BACKGROUND
PMID: 21693744 (View on PubMed)

Puurunen J, Piltonen T, Puukka K, Ruokonen A, Savolainen MJ, Bloigu R, Morin-Papunen L, Tapanainen JS. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013 Dec;98(12):4798-807. doi: 10.1210/jc.2013-2674. Epub 2013 Oct 23.

Reference Type BACKGROUND
PMID: 24152688 (View on PubMed)

Duvnjak L, Blaslov K. Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study. J Clin Lipidol. 2016 Jul-Aug;10(4):1004-1010. doi: 10.1016/j.jacl.2016.04.012. Epub 2016 May 10.

Reference Type BACKGROUND
PMID: 27578133 (View on PubMed)

Chapple CR, Dvorak V, Radziszewski P, Van Kerrebroeck P, Wyndaele JJ, Bosman B, Boerrigter P, Drogendijk T, Ridder A, Van Der Putten-Slob I, Yamaguchi O; Dragon Investigator Group. A phase II dose-ranging study of mirabegron in patients with overactive bladder. Int Urogynecol J. 2013 Sep;24(9):1447-58. doi: 10.1007/s00192-013-2042-x. Epub 2013 Mar 8.

Reference Type BACKGROUND
PMID: 23471546 (View on PubMed)

Loeliger RC, Maushart CI, Gashi G, Senn JR, Felder M, Becker AS, Muller J, Balaz M, Wolfrum C, Burger IA, Betz MJ. Relation of diet-induced thermogenesis to brown adipose tissue activity in healthy men. Am J Physiol Endocrinol Metab. 2021 Jan 1;320(1):E93-E101. doi: 10.1152/ajpendo.00237.2020. Epub 2020 Nov 23.

Reference Type DERIVED
PMID: 33225717 (View on PubMed)

Fischer JGW, Maushart CI, Becker AS, Muller J, Madoerin P, Chirindel A, Wild D, Ter Voert EEGW, Bieri O, Burger I, Betz MJ. Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity. EJNMMI Res. 2020 Jul 22;10(1):85. doi: 10.1186/s13550-020-00665-7.

Reference Type DERIVED
PMID: 32699996 (View on PubMed)

Other Identifiers

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FluvaBAT

Identifier Type: -

Identifier Source: org_study_id